UPMC Physician Resources

Pitt Cancer Institute Researchers Say Decoy Shows Promise as Cancer-Fighter in Novel Phase 0 Trial

Posted by andrewsj3 on Friday, August 10th 2012     
PITTSBURGH, August 10, 2012 – A critical protein that had been deemed “undruggable” can be effectively targeted by using a decoy to fool the body into a cancer-fighting response, according to researchers at the University of Pittsburgh Cancer Institute (UPCI) and the University of Pittsburgh School of Medicine. In a report in the August issue of Cancer Discovery, they showed the decoy was successful in a phase 0 study, an uncommon but useful preface to the commencement of standard human trials.
 
Activation and increased signaling of a protein known as Signal Transducer and Activator of Transcription 3 (STAT3) has been identified in many cancers and is associated with poor prognosis, said senior author Jennifer Grandis, M.D., professor of otolaryngology and pharmacology and chemical biology, Pitt School of Medicine, and director of the Head and Neck Program at the University of Pittsburgh Cancer Institute (UPCI). Transcription factors such as STAT3 regulate the activity, or expression, of other genes; in adult tissues, STAT3 triggers the production of other proteins that promote the growth and survival of cancer cells.
 
“Lab experiments have shown that inhibiting STAT3 activity or function limits the proliferation and survival of a variety of cancer cell lines,” she explained. “But the drugs that have been tested in patients are not selective for STAT3 and haven’t been effective.”
 
So her research team tried an unusual approach: they fooled the STAT3 protein into binding to a harmless decoy that they engineered, rather than the real gene sequence that would have initiated the production of cancer-promoting proteins. Preclinical experiments showed that the strategy was tolerated well and didn’t produce toxic side effects.
 
To further justify clinical development, the team conducted a phase 0 study to see if the decoy would work in humans. First, they took biopsies of head and neck cancers in 30 patients who were having surgery to remove the tumors. At the start of the operation, the tumors were injected with either the decoy or a salt-water placebo. After surgery, about four hours after injection, the cancerous tissue that had been taken out of each patient was biopsied again. Tests were conducted in the specimens to determine the activity of genes regulated by STAT3.
 
“We found reduced expression of the STAT3 target genes in tumors that had been treated with the decoy compared to those that got a placebo injection and to pre-treatment samples,” Dr. Grandis said. “This indicates we were able to selectively inhibit STAT3, which is a significant step forward.”
 
The researchers also developed a version of the decoy that could be injected into the bloodstream, which inhibited tumor growth in a mouse model of head and neck cancer.
 
Co-authors of the paper include researchers from the departments of Otolaryngology, Structural Biology, Bioengineering, Medicine, Pharmacology and Chemical Biology, Pathology and Biostatistics at the University of Pittsburgh; Carnegie Mellon University, The Ohio State University; and the University of Texas M.D. Anderson Cancer Center.
 
The project was funded by grants GM068566 and CA137260 of the National Institute of General Medical Services, part of the National Institutes of Health, the American Cancer Society and the PNC Foundation. Dr. Grandis receives research support for Bristol-Myers Squibb.
category: Cancer
tags: , , , , , , ,

Life Expectancy Increasing for Type 1 Diabetics, According to Latest Pitt Research

Posted by andrewsj3 on Friday, August 10th 2012     
PITTSBURGH, August 10, 2012 – The life expectancy of people diagnosed with type 1 diabetes dramatically increased during the course of a 30-year, long-term prospective study, according to researchers at the University of Pittsburgh whose findings currently appear online in the journal Diabetes.
 
The life expectancy for participants diagnosed with type 1 diabetes between 1965 and 1980 was 68.8 years – a 15-year improvement, compared to those diagnosed between 1950 and 1964, according to the study. Meanwhile, the life expectancy of the general U.S. population increased less than one year during the same time period.
 
“The estimated 15-year life expectancy improvement between the two groups persisted regardless of gender or age at diagnosis,” said Rachel Miller M.S., statistician at the University of Pittsburgh Graduate School of Public Health and lead author of the study.
 
 The results are based on participants in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, a long-term prospective study of childhood onset type 1 diabetes, which began in 1986. Participants, who were an average age of 28 when entering the study and 44 at its completion, were diagnosed with type 1 diabetes between 1950 and 1980.
 
“Type 1 diabetes mortality rates are known to have decreased over time, but recent life expectancy estimates for those diagnosed with type 1 diabetes in the United States are lacking,” said Trevor Orchard MD, senior author and professor of epidemiology, pediatrics and medicine at the University of Pittsburgh. “Therefore, we estimated life expectancy of the EDC study cohort and were impressed to see such an improvement – a tribute to how modern day treatment has dramatically changed the outlook for those with childhood onset type 1 diabetes.”
 
The 30-year mortality of participants diagnosed with type 1 diabetes from 1965 to 1980 was 11.6 percent – a significant decline from the 35.6 percent 30-year mortality of those diagnosed between 1950 and 1964, according to the study.
 
Previously known as juvenile diabetes, type 1 diabetes is usually diagnosed in children and young adults. In type 1 diabetes, the pancreas produces little or no insulin to properly control blood sugar levels. It is typically treated with insulin replacement therapy.
 
In addition to Dr. Orchard, other authors include Aaron M. Secrest, Ph.D.; Ravi K. Sharma, Ph.D.; and Thomas J. Songer, Ph.D., all of the University of Pittsburgh. The study was funded by the National Institutes of Health.

Brian J. Druker, M.D., Will Receive Pitt’s Dickson Prize at Science 2012— Translation

Posted by andrewsj3 on Wednesday, August 8th 2012     
PITTSBURGH, Aug. 8, 2012 – An internationally known cancer researcher who developed a drug for the treatment of chronic myeloid leukemia (CML) has been named this year’s recipient of the University of Pittsburgh’s Dickson Prize in Medicine.
 
Brian J. Druker, M.D., will accept the University of Pittsburgh School of Medicine’s most prestigious honor during Science 2012—Translation, a showcase of the region’s latest research in science, engineering, medicine, and computation that will be held on Oct. 3 through 5 at Alumni Hall, Oakland. Dr. Druker is director and JELD-WEN chair of leukemia research at the Oregon Health and Science University Knight Cancer Institute and a Howard Hughes Medical Institute investigator.
 
“Dr. Druker’s work revolutionized the development of cancer treatment by showing that an understanding of the molecular pathogenesis of this disease can lead to targeted drug development. This is a powerful example of taking science from the laboratory to the bedside. We are pleased to honor Dr. Druker with the Dickson Prize for his tremendous contribution to medicine,” said Arthur S. Levine, M.D., Pitt’s senior vice chancellor for the health sciences and dean, School of Medicine.
 
On Thursday, Oct. 4, at 11 a.m., Dr. Druker will deliver the Dickson Prize in Medicine Lecture. His talk is titled “Imatinib as a Paradigm of Molecularly Targeted Cancer Therapies.”  Dr. Druker led the development of imatinib, also known as Gleevec, which is approved for use with CML, gastrointestinal stromal tumors, and five other cancers. His current research projects are aimed at learning why a small percentage of CML patients develop resistance to Gleevec and why most patients on the drug have minute levels of cancer that linger, even after successful treatment. His laboratory is also working to identify the molecular defects that drive the growth of other leukemias and to use this information to develop new, targeted treatments to improve the outcomes for patients with these leukemias.
 
Other renowned researchers also will deliver plenary lectures at Science 2012:
 
Provost Lecture, 4 p.m., Thursday, Oct. 4
  • “Sustainable Energy Innovators: Moving Toward a Low-Carbon Future” presented by Miranda A. Schreurs, Ph.D., director of the Environmental Policy Research Centre and professor of comparative politics at the Freie Universität Berlin. Dr. Schreurs specializes in science and politics, and her work focuses on comparative environmental politics and policy in the U.S., Europe, and East Asia. 
Mellon Lecture, 11 a.m., Friday, Oct. 5
  • “Riboswitches: Biology’s Ancient Regulators” presented by Ronald R. Breaker, Ph.D., chair of the Department of Molecular, Cellular and Developmental Biology at Yale University and a Howard Hughes Medical Institute investigator. As a postdoctoral researcher at the Scripps Research Institute, Dr. Breaker pioneered a variety of “test-tube evolution” strategies to isolate novel RNA enzymes and was the first to discover catalytic DNAs or “deoxyribozymes” using this technology. He co-founded Archemix, a biotechnology company that developed engineered RNA sensors and aptamers for therapeutic applications, and cofounded BioRelix, a biotechnology company developing antibiotics that target bacterial riboswitches.
Klaus Hofmann Lecture, 4 p.m., Friday, Oct. 5
  • “Optogenetics: Development and Application” presented by Karl Deisseroth, M.D., Ph.D., an associate professor of bioengineering and psychiatry at Stanford University and a Howard Hughes Medical Institute early career scientist. Dr. Deisseroth pioneered the development and application of optogenetics, a technology that uses light to control millisecond-precision activity patterns in genetically defined cell types within the brains of freely moving mammals.

Urine Test Can Indicate a Woman’s Risk of Bone Fracture, Pitt Study Finds

Posted by andrewsj3 on Wednesday, August 1st 2012     
PITTSBURGH, Aug. 1, 2012 – A simple urine test can indicate a premenopausal woman’s risk of suffering bone fractures as she ages, according to new research led by University of Pittsburgh Graduate School of Public Health (GSPH) epidemiologists.
 
Women in their 40s and early 50s had a 59 percent greater risk of bone fracture as they aged when they had above-normal levels of N-telopeptide (NTX) – the byproduct of bones breaking down – in their urine, compared with women who had low NTX levels. When women with high NTX levels also had a low spinal bone density measurement, their risk of fracture increased nearly three-fold.
 
The study is the first to look for signs of bone breakdown in younger, premenopausal women in an effort to determine if such signs can predict the risk that these women will suffer fractures as they age.
 
The results were published today in the online edition of Menopause, the journal of The North American Menopause Society. The report will be published in the journal’s November print issue.
 
“Bone fractures – particularly in the hip, wrist and back – have serious consequences, including disability and death,” said Jane Cauley, Dr.P.H., professor of epidemiology, GSPH, and lead author of the study. “Knowing a woman’s risk of fracture can help doctors determine the best course of action to protect her bones as she enters menopause, a time when estrogen deficiency negatively affects skeletal health.”
 
By the time a woman turns 50, her risk of a fracture at some point in the remainder of her life is estimated to be at least 40 percent. Fractures are more common for these women than heart attacks, strokes and breast cancer combined.
 
During menopause, bone remodeling increases, leading to an imbalance between bone formation and bone resorption, or the process by which bones are broken down and their minerals are returned to the blood. This remodeling persists for several years and is associated with an increased rate of bone loss, making it easier for bones to fracture.
 
Cauley and her colleagues used data from 2,305 premenopausal or perimenopausal women aged 42 to 52 collected over an average of 7.6 years as part of the Study of Women’s Health Across the Nation (SWAN). Participants were from Boston, Detroit, Los Angeles, Pittsburgh and Oakland, Calif.
 
SWAN examines the physical, biological, psychological and social health of women during their middle years. The goal is to help scientists, health care providers and women learn how mid-life experiences affect health and quality of life during aging.
 
Collaborators on this study include Michelle E. Danielson, Ph.D., Yue-Fang Chang, Ph.D., Kristine Ruppert, Dr.P.H., Leslie Meyn, M.S., and Beth A. Prairie, M.D., M.S., all of the University of Pittsburgh; Gail A. Greendale, M.D., and Carolyn J. Crandall, M.D., M.S., both of the University of California Los Angeles; Joel S. Finkelstein, M.D., and Robert M. Neer, M.D., both of Massachusetts General Hospital; Joan C. Lo, M.D., of Kaiser Permanente Northern California; and MaryFran R. Sowers, Ph.D., of the University of Michigan.
 
This research was supported by the National Institutes of Health (NIH), Department of Health and Human Services, through the National Institute on Aging, the National Institute of Nursing Research and the NIH Office of Research on Women’s Health (grants NR004061, AG012495, AG012505, AG012531, AG012553 through AG012535, AG012539 and AG012546). This work also was supported by Department of Defense grant DAMD17-96-6118; NIH grants K24-DK02759 and RR-1066; the Iris Cantor-University of California, Los Angeles Women’s Health Center; and University of California, Los Angeles Center of Excellence in Women’s Health grant RFP 282-97-0025. 

Pitt Researchers Pinpoint Peptide that Blocks Hepatitis C Virus Entry

Posted by andrewsj3 on Tuesday, July 31st 2012     
PITTSBURGH, July 31, 2012 – Researchers at the University of Pittsburgh’s Graduate School of Public Health (GSPH) have identified a specific peptide that may block the entry of the hepatitis C virus (HCV) into the liver, representing  a potential target for new drug development.
 
The results are available online now and will be published in the August 2012 print edition of Hepatology, the official journal of the American Association for the Study of Liver Disease. 
 
“Viral entry is a multi-step process, involving a number of host factors; therefore, these findings represent a promising target for new antiviral drugs,” said Tianyi Wang, Ph.D., associate professor, Department of Infectious Diseases and Microbiology, GSPH, and the study’s lead author.
 
Previous research indicates that human apolipoprotein E (apoE), which occurs naturally in the body, forms complexes with HCV, the scientists said. They constructed peptides, dubbed hEP, containing the portions of apoE to which other proteins and lipids typically bind.
 
In lab tests, they found that hEP blocked the virus from binding to liver cells, preventing infection. That suggests apoE is involved with HCV’s initial entry into the cells, Dr. Wang said. It’s possible that hEP thwarts infection because it competes with HCV for a cell surface receptor. 
 
In addition, researchers determined that the ability of hEP to block the virus appears to be dependent on the peptide’s length and sequence. Shorter versions could not stop infection, possibly because the shape of the proteins—and thus their binding ability—was altered.
 
“Our findings highlight the potential of developing peptides that mimic hEP as new hepatitis C viral inhibitors,” said Dr. Wang.
 
Worldwide, more than 170 million people are infected with the hepatitis C virus, which often is asymptomatic and can cause severe liver disease and liver cancer. There is no cure for HCV and no vaccine. Existing treatments are effective in only 40 percent to 80 percent of patients and can cause severe side effects.   
 
Despite the recent U.S. Food and Drug Administration approval of two new antiviral drugs designed to treat chronic HCV infection, patients may rapidly develop resistance. Much like current HIV therapies, successful treatment of HCV may involve multiple inhibitors of different targets, researchers said. 
 
“New antiviral drugs are urgently needed to treat HCV infection independently, or in combination with current therapies,” said Dr. Wang.
Collaborators on the studies include Shufeng Liu, Ph.D., and Kevin D. McCormick, M.S., Department of Infectious Diseases and Microbiology, GSPH, University of Pittsburgh; Wentao Zhao, Ph.D., and Daping Fan, Ph.D., Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina; and Ting Zhao, Department of Pathology, University of Pittsburgh School of Medicine.
 
The research was funded by grants R21AI083389, R01DK088787, and R21HL106325 from the National Institutes of Health.

Pitt Researchers Developing Liver and Joint “Tissue Chips” to Better Predict Drug Safety

Posted by andrewsj3 on Friday, July 27th 2012     
PITTSBURGH, July 27, 2012 – Researchers at the University of Pittsburgh School of Medicine have been awarded federal grants to create micro-models of the liver and an arthritic joint as part of a national effort to build 3-D chips of cells and tissues that could  provide a more rapid and accurate method of predicting toxicity of experimental therapies, as well as foster greater understanding of myriad diseases.
 
Of the 17 projects being funded by the National Institutes of Health (NIH), two will be led by Pitt researchers and could receive more than $10 million over the next five years. NIH plans to commit up to $70 million over five years for the Tissue Chips for Drug Screening program, which was launched by its new National Center for Advancing Translational Sciences (NCATS). Other awardees include Johns Hopkins University, Harvard University and Duke University.
 
“Tissue chips could provide a more accurate and less expensive way of testing new drugs and reduce our reliance on animal studies, which often don’t reliably reflect toxicity profiles later seen during human testing,” noted Arthur S. Levine, M.D., senior vice chancellor for the health sciences and dean, Pitt School of Medicine. “It is terrific that our stellar scientists will be able to build two of these chips here and contribute to the evolution of drug testing.”
 
The Pitt projects are:
 
  • 3-D Micro-Liver: D. Lansing Taylor, Ph.D., Allegheny Foundation Professor of Computational and Systems Biology, and director, University of Pittsburgh Drug Discovery Institute, will lead a team at Pitt and Massachusetts General Hospital to create a three-dimensional microfluidic structure made entirely of human cells that will mimic the acinus, the smallest functional unit of the liver. The team also will develop a panel of sentinel “biosensor cells” that will indicate liver toxicity with exposure to different drugs.
  • The current gold standard of testing is not very gold,” Dr. Taylor said. “In humans, the liver plays a key role in processing drugs, and many experimental agents have failed in the late stages of human testing because preclinical studies didn’t predict their impact on the liver, along with other organs. This project aims to solve that problem so that we have greater success in drug discovery and development.”
  • 3-D Micro-Arthritic Joint System: Rocky Tuan, Ph.D., the Arthur J. Rooney Sr. Professor of Sports Medicine and executive vice chair for research, Department of Orthopaedic Surgery, will lead a team to create a tissue chip that includes stem cell-produced bone and cartilage cells that simulate joint surfaces to better understand how arthritis develops and how to prevent it.
  • This system will allow us to explore the effects of not only inflammatory molecules and the wear-and-tear of aging on the entire joint, but also mechanical injuries, such as a hit or a sprain, both immediately and over time in molecular detail, which is not feasible with existing techniques,” said Dr. Tuan, who also is director of the Center for Military Medicine Research, director of the Center for Cellular and Molecular Engineering in the Department of Orthopaedic Surgery, and co-director of the McGowan Institute for Regenerative Medicine.

According to NIH, the Tissue Chips program is the result of collaboration between NIH, the Defense Advanced Research Projects Agency (DARPA) and the U.S. Food and Drug Administration, and was established by the NIH’s Common Fund and the National Institute of Neurological Disorders and Stroke.

“Serious adverse effects and toxicity are major obstacles in the drug development process,” said Thomas R. Insel, M.D., NCATS acting director. “With innovative tools and methodologies, such as those developed by the Tissue Chips program, we may be able to accelerate the process by which we identify compounds likely to be safe in humans, saving time and money, and ultimately increasing the quality and number of therapies available for patients.”

Drs. Taylor and Tuan’s projects also will receive support from the University of Pittsburgh Clinical and Translational Science Institute.

Pitt Researchers Obtain $4.5 Million Grant to Study Potential Improvements for Wheelchair Users

Posted by andrewsj3 on Thursday, July 26th 2012     
PITTSBURGH, July 26, 2012 – Researchers from the University of Pittsburgh School of Medicine and UPMC will lead a five-year, multi-site project aimed at improving the lives of people with Spinal Cord Injuries (SCI). The study will use Internet-based training and group sessions to hone the skills of wheelchair use and prevent wheelchair failures. This research will involve more than 500 participants over four different sites, making it one of the largest studies of its kind.
 
Among the other groups involved in the research are: the Northern New Jersey Spinal Cord Injury System, a cooperative effort of the Kessler Foundation, the Kessler Institute for Rehabilitation and the University of Medicine and Dentistry of New Jersey; the Midwest Regional Spinal Cord Injury Care System, which brings together Northwestern University’s Feinberg School of Medicine and the Acute Spinal Cord Injury Program at Northwestern Memorial Hospital, plus the Spinal Cord Injury Rehabilitation Program at the Rehabilitation Institute of Chicago; and the University of Miami Miller School of Medicine’s Department of Rehabilitation Medicine and The Miami Project, along with Jackson Memorial Hospital forming the South Florida Spinal Cord Injury System.
 
“This grant will start to tackle problems related to insurance cutbacks that have negatively impacted individuals with Spinal Cord Injuries,” said Michael Boninger, M.D., professor and chair, Department of Physical Medicine and Rehabilitation, Pitt School of Medicine. “Because they spend less time in the hospital after their injuries, they never learn how to effectively use and maintain their wheelchairs. We need an effective, low-cost way to provide people with training that maximizes their independence – this study tackles that problem.”
 
Through the efforts of Pitt’s Department of Physical Medicine and Rehabilitation; the School of Health and Rehabilitation Sciences; the UPMC Rehabilitation Institute; and the Human Engineering Research Laboratories – a joint Pitt, UPMC and VA project – Pittsburgh has become nationally and internationally recognized for its expertise in technologies for persons with disabilities.
 
The latest grant – from the National Institute for Disability and Rehabilitation Research — comes barely two months after a published Pitt-UPMC study, with Boninger as the senior author, found 52 percent of people with SCI required wheelchair repairs in the preceding six months. Many of the wheelchair users who needed repairs experienced adverse consequences, the study also found. The same set of Pitt-UPMC researchers also have a 2012 study paper accepted for publication finding a relationship between the ability to perform wheelchair skills – after training – and higher life satisfaction and community participation. The abstract is available at http://www.ncbi.nlm.nih.gov/pubmed/22684049.

Most U.S. Cities That Prohibit Smoking in Bars Allow Hookah Smoking, Pitt Study Finds

Posted by andrewsj3 on Wednesday, July 25th 2012     
PITTSBURGH, July 25, 2012 – Nearly 90 percent of the largest U.S. cities that prohibit cigarette smoking in bars have exemptions that permit hookah smoking despite the health risks of this increasingly popular form of tobacco consumption, according to a new study from researchers at the University of Pittsburgh School of Medicine that appears in an upcoming issue of the American Journal of Public Health and is available online now.
 
Hookah tobacco smoking is becoming more common in the U.S., especially among college-aged students, but few people are aware of the health risks, said Brian Primack, M.D., Ph.D., associate professor of medicine and pediatrics and director of the Program for Research on Media and Health at Pitt’s School of Medicine, who led the study. The World Health Organization found that a hookah smoker may inhale as much smoke during a hookah smoking session as someone would from smoking 100 cigarettes, and studies have suggested secondhand smoke from hookah is also a concern.
 
“There is a growing body of scientific evidence that suggests real health risks associated with hookah tobacco smoking. And although clean air policies have led to a decrease in cigarette smoking in the U.S., there are still few policies that address smoking tobacco through a hookah,” Dr. Primack said.
 
Researchers assessed tobacco-related clean air policies for each of the 100 most populous U.S. cities based on 2010 census data. The policies were part of the US Tobacco Control Laws Database, which is maintained by the California-based American Nonsmokers’ Rights Foundation.
 
They found that 73 of the 100 largest cities in the U.S. have laws that disallow cigarette smoking in bars. However, 69 of those cities have exemptions that may allow hookah smoking. Many of the policies designed to clean air and discourage tobacco use were enacted before hookah smoking’s popularity.
 
“As hookah smoking grows more widespread, we believe it’s a good idea for lawmakers, health policy officials and others to take a closer look at clean air policies and how they relate to hookah-tobacco smoking, given the health risks,” Dr. Primack said.
 
Collaborators on the study were Mary V. Carroll, B.A., and Michael J. Fine, M.D., M.Sc., both of the University of Pittsburgh School of Medicine; Maggie Hopkins, B.A., and Cynthia Hallett, M.P.H., both of the American
Nonsmokers’ Rights Foundation; Mitchell Zeller, J.D., of Pinney Associates, Bethesda, Md.; Kathleen Dachille, J.D., of the Francis King Carey School of Law, University of Maryland, Baltimore; Kevin H. Kim, Ph.D., of the University of Pittsburgh School of Education; and Julie M. Donohue, Ph.D., with the University of Pittsburgh Graduate School of Public Health.
 
The study was funded by the National Cancer Institute.

Antibiotic that Works in Low-Oxygen Setting Prevents Reactivation of TB Infection, Says Pitt Team

Posted by andrewsj3 on Monday, July 23rd 2012     
PITTSBURGH, July 23, 2012 – Reactivation of latent tuberculosis infection could be better prevented if a drug that is effective against bacteria in low-oxygen environments is added to the treatment regimen, according to researchers at the University of Pittsburgh School of Medicine in this week’s online Early Edition of the Proceedings of the National Academy of Sciences.
 
Pulmonary TB is spread through infected air droplets, said senior author JoAnne L. Flynn, Ph.D., professor, Department of Microbiology and Molecular Genetics, Pitt School of Medicine. People can develop active TB with cough, fever, night sweats and fatigue, but most develop an asymptomatic “latent” infection where the bacteria, called Mycobacterium tuberculosis, can remain in the lung tissue walled off in a lesion called a granuloma. In some, particularly the elderly or immune-compromised, the infection can reactivate years later.
 
“An estimated 2 billion people worldwide are latently infected with TB, so it’s imperative to have treatment strategies that can prevent the disease from becoming active again,” Dr. Flynn said. “The infection reactivates in about 10 percent of patients with healthy immune systems, and each case of infectious TB can lead to more than seven new cases. ”
 
Currently, active TB that is not resistant to antibiotics is treated with a so-called “short course” of two months of the drugs isoniazid (INH), rifampin (RIF), pyrazinamide and ethambutol, followed by four more months of INH and RIF. Latent infection is treated with nine months of INH, which acts primarily on replicating bacteria. It’s challenging for patients to continue the treatments to their conclusion, so new drugs that act more quickly would be very helpful, noted Dr. Flynn, who also is an associate member of the University of Pittsburgh’s Center for Vaccine Research.
 
Previous research has shown that the TB bacilli that can survive low-oxygen conditions are not susceptible to INH. Yet the caseous (“cheese-like”) granulomas commonly seen in human infection have areas of tissue death, or necrosis, associated with a hypoxic environment. That led the team to examine whether metronidazole (MTZ), an antibiotic that is known to be effective against non-replicating bacteria in low-oxygen settings, would be better able to eradicate the TB bacilli contained in the granuloma.
 
The researchers found that in a macaque model of TB, two months of MTZ alone was as effective as two months of INH and RIF at preventing reactivation of the infection induced by an agent called anti-tumor necrosis factor antibody, which triggered disease in most of the untreated animals. Also, adding MTZ to an INH and RIF regimen reduced bacterial burden in monkeys with active TB within two months.
 
“Instead of merely active or latent, TB can be considered a spectrum of the same disease related to bacterial burden,” Dr. Flynn said. “The next step is to find better drugs that work in these hypoxic areas of granulomas because MTZ can be difficult to tolerate over an extended time.”
 
Co-authors of the paper include Philana Ling Lin, M.D., Children’s Hospital of Pittsburgh of UPMC; Veronique Dartois, Ph.D., Novartis Institute for Tropical Diseases, Singapore; Paul J. Johnston, Department of Microbiology and Molecular Genetics, Pitt School of Medicine; Christopher Janssen, D.V.M., and Edwin Klein, D.V.M., Division of Laboratory Animal Research, University of Pittsburgh; and Laura Via, Ph.D., Michael B. Goodwin, and Clifton E. Barry III, Ph.D., all of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.
 
The project was funded by the Bill and Melinda Gates Foundation Grand Challenge 11 “Drugs for Latent TB”; the Otis Foundation; and, in part, by the Intramural Research Program of NIAID.

Pitt Scientists Developing Universal Flu Vaccine in Partnership with Sanofi Pasteur

Posted by andrewsj3 on Thursday, July 19th 2012     
PITTSBURGH, July 19, 2012 – A vaccine strategy that protects against all strains of seasonal influenza and avoids the need for annual vaccination is the ultimate goal of a research collaboration between the University of Pittsburgh and vaccine-maker Sanofi Pasteur.
 
Ted M. Ross, Ph.D., and his laboratory scientists at the University of Pittsburgh’s Center for Vaccine Research (CVR) are exploring new vaccine technologies intended to protect against all strains of seasonal influenza and be made in less than half the time of the traditional flu shot. The vaccine could potentially cover influenza strains circulating over multiple seasons, eliminating the need for a seasonal flu shot. 
 
“Our vaccine is adaptable to any delivery method, whether it is a needle to the arm or a nasal spray,” said Dr. Ross, associate professor of microbiology and molecular genetics, School of Medicine, and a CVR scientist. “It would protect against whatever strain of seasonal flu happens to be circulating, and it can be produced in as little as four months.”
 
Pursuant to the sponsored research agreement, Sanofi Pasteur will have exclusive access to the University of Pittsburgh’s vaccine technology and will have an option to worldwide exclusive development and commercialization rights to any resulting influenza vaccine.
 
The University of Pittsburgh’s CVR scientists will work directly with scientists at Sanofi Pasteur, the world’s top influenza vaccine maker and a division of Sanofi, one of the world’s largest pharmaceutical companies. The agreement demonstrates the University of Pittsburgh’s commitment to develop meaningful partnerships with industry.
 
“This project will have a tremendous impact here and around the world,” said Arthur S. Levine, M.D., University of Pittsburgh senior vice chancellor for the health sciences and dean, School of Medicine. “Many people will embrace the opportunity of getting a single shot of vaccine to prevent flu — and its potentially deadly consequences – for a lifetime. With this outstanding effort, the CVR has accomplished its mission of improving health on a global scale by studying the world’s most dangerous infections.”
 
 
“The University of Pittsburgh is where Dr. Jonas Salk pioneered the polio vaccine, and the university continues to be a leader in vaccine research,” said Dr. Burke, UPMC-Jonas Salk Chair of Global Health. “The seasonal influenza vaccine that our CVR scientists are developing could do to the flu – and the thousands of people who die from it annually – what Dr. Salk and his team did to polio.”
 
The U.S. Centers for Disease Control and Prevention (CDC) estimates that annual flu-associated deaths in the United States range from 3,000 to 49,000, depending on the severity of the virus. The CDC has stated that, in the next five years, it wants vaccine manufacturers to create improved seasonal flu vaccines that cover more strains. 
 
While the traditional flu vaccine uses a mix of inactivated viruses, the experimental shot would be a synthetic vaccine created from the genetic sequence of flu viruses. Termed “computationally optimized broadly reactive antigen,” or COBRA, the method would produce protection against all strains of seasonal influenza, including those not yet in existence. So, the synthetic flu shot may also be effective far longer than the traditional flu vaccine.
 
Dr. Ross previously used the COBRA method to produce a vaccine against bird flu, or H5N1. This vaccine successfully protects against all known strains of bird flu and has been well-tolerated in pre-clinical trials.
 
The traditional seasonal flu vaccine takes nearly a year to create. Each year at the conclusion of flu season, world health officials meet to select the three strains of flu they believe are most likely to circulate in the coming fall and winter. If they choose the wrong strains, the seasonal flu shot is less effective.
 
The strains of flu that circulate every year can exchange genes with one another and with some animal influenza viruses. This reshuffling of genes means that new flu strains emerge each year. Health officials must then capture, inactivate and grow these new strains into the seasonal flu vaccine. Because the synthetic vaccine is created using the genes that make up flu viruses, this reshuffling is already accounted for and the vaccine could protect against millions of different flu strains.
 
For the next two to four years, the University of Pittsburgh’s seasonal flu vaccine will be in pre-clinical trials. If successful, the vaccine could then enter FDA clinical trials in humans. Each stage of the project will be evaluated by the University of Pittsburgh-Sanofi Pasteur joint steering committee.
 
If all goes well, the new vaccine could potentially replace the seasonal flu vaccine in about a decade.
 
A video of Dr. Ross discussing his vaccine technology research is available at http://www.youtube.com/watch?v=uLBfoOvBXfo&feature=youtu.be.
Page 9 of 24:« First« 6 7 8 9 10 11 12 »Last »